These studies seek to define and describe the molecular mechanisms whereby the major catabolic (i.e. energy-releasing) pathways of intermediary metabolism are controlled, and to investigate the ways in which these controls are altered in old-age. Such alterations are considered to underlie the decreased ability of senescent animals (including humans) to withstand environmental stresses (e.g. starvation, severe cold). Current investigations feature: (1) the control of pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase activities by micromolar concentrations of Ca++ ions; (2) the transport of Ca++ ions into the out of heart mitochondria and its relation to the homeostasis of cytosolic free Ca++ concentrations; (3) the control of pyruvate dehydrogenase in skeletal muscle mitochondria and the effect of fatty acid and ketone oxidation; and (4) the impact of aging upon the transfer of cytosolic reducing equivalents into heart mitochondria by means of the malate/aspartate shuttle.